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Dr Penny Neild
Chelsea and Westminster Hospital
London, UK
It is likely that many thousands of people worldwide are leading their lives unaware that they are HIV seropositive. Obviously this has implications, both for the care that they perhaps should be receiving, and the risk of further transmission of the virus through ignorance of their own infectivity. It is crucial in this era for us as medical practitioners to be vigilant and recognize the outward manifestations of a failing immune system in order that we can make a diagnosis of HIV infection sooner rather than later. Most opportunistic infections only occur in the setting of advanced immune suppression, and these will be addressed separately. However many conditions, some apparently trivial and common in the general population, may present slightly differently or with increased severity in HIV infected individuals, and should raise the possibility of immune compromise.
This may be asymptomatic, but up to 90% of individuals who have contracted HIV will undergo symptoms during seroconversion.
During this period, the immune system becomes acutely compromised, often with a dramatic fall in CD4 count which may lead to development of opportunistic infections more often associated with AIDS e.g. oesophageal candida, PCP.
The most common symptoms occur 2-6 weeks after exposure to the virus when the HIV antibody test would still be negative though p24 antigenaemia would be detectable. These include influenza-like illness with fevers, myalgia, and tender lymphadenopathy. A rash may develop during or up to a week after such symptoms, with red non-itchy lesions scattered widely over the body, limbs, palms and soles and sometimes associated oral ulceration. The differential diagnosis includes infectious mononucleosis, pityriasis rosea, secondary syphilis, drug reaction, or toxic erythema due to another infectious cause.
1) Psoriasis
This is probably not increased in prevalence but may become worse or appear for the first time during HIV infection. Psoriasis manifesting after development of HIV infection appears slightly different in character with more common involvement of palms and soles and associated arthritis, similar to Reiters syndrome. Family history of psoriasis is also less common in this group.
2) Drug allergies
HIV infection is associated with a nonspecific polyclonal gammopathy as result of diminished T cell control of B cell function. The ensuing atopic state with hyper-responsiveness to allergens leads to increased risk of adverse reactions to drugs with allergies more common during early and particularly middle periods of HIV infection. With severe immunodepression, capability of mounting such a response diminishes.
3) Molluscum contagiosum
These pox virus-associated hard cream coloured umbilicated papules may be seen in on the skin of atopic children, or more sparsely as a venereal infection around the normal adult perineum. In HIV infection, as the CD4 count declines below 100, scores of mollusca may appear, often on the face and mantle area.
4) Viral warts
Human papilloma virus is a common skin pathogen in HIV infection, and the resulting often multiple verrucous warts are difficult to treat.
5) Seborrhoeic dermatitis
This common skin condition, characterized by erythematous scaly patches ofskin, most commonly in the malar region, nasolabial fold, eye brows, scalp, and behind the ears occurs in about 3% of the general population. Among HIV infected persons, the prevalence is vastly increased, ranging from 7-50%. Both the frequency and severity are closely related to the stage of HIV infection.
6) Premature aging
HIV accelerates the aging process and can induce premature common baldness. Malabsorption can result in diffuse hair thinning due to deficiency of iron, protein or essential fatty acids.
1) Buccal candidiasis
Though this can be seen in the general population in association with conditions such as diabetes or concurrent antibiotic or steroid therapy, the presence of oral candida in the absence of the above is suggestive of immune suppression, e.g. HIV infection.
2) Oral hairy leukoplakia
With the exception of a few cases observed in transplant recipients, this Epstein-Bar virus related condition, with its dramatic white corrugations on the side of the tongue is confined to HIV disease- and thus highly suggestive of seropositivity. Sometimes confused with candida, it is usually asymptomatic, cannot be scraped off, and does not respond to anti-fungal medication.
3) Gingivitis
Periodontal disease including gingivitis and gum recession is frequently seen in HIV disease and may be extremely aggressive, leading to tooth loss and bone destruction.
Skin
Bacterial skin infections are more common in HIV disease. Worsening acne is often seen. Infections may present as folliculitis, a localized abscess or ulcer, secondary infection of other skin lesions (e.g. herpes) or as cellulites.
Pneumonia
Bacterial pneumonia occurs with increased frequency in patients with HIV infection and AIDS. The majority of cases are due to Strep pneumoniae, Haemophilus influenzae and, in later disease, Pseudomonas aeruginosa though a large number of pathogenic or opportunistic bacteria may cause pneumonia in these patients. The clinical manifestations of bacterial pneumonia in these patients generally are similar to those in immunocompetent hosts, with fever, cough productive of purulent sputum, and proportion of patients with pneumonia due to pyogenic bacteria develop bacteraemia, and the course of the illness may be more severe and prolonged than in immunocompetent hosts. Recurrent episodes, not necessarily due to the same pathogens, may occur.
Tuberculosis
The worldwide epidemic of HIV infection has resulted in a major secondary epidemic of TB. Most of the cases of active TB among persons infected with HIV represent re-activation of latent tuberculous infection rather than the progression of recently acquired infection. Early in HIV infection TB usually presents in a typical clinical form, whereas late in HIV disease, after AIDS has already been diagnosed, subtle and atypical presentations are more common. Although pulmonary disease still predominates extrapulmonary disease, often lymphatic or haematogenously disseminated, with or without co-existing pulmonary TB may appear in 40-75% of patients with both diagnosis. Because of the strong association of active TB with HIV infection, the Centres for Disease Control (CDC) recommends that all patients with TB should be offered counseling and HIV antibody testing, especially in individuals with extrapulmonary disease, and persons in the demographic and risk groups in which the overlap of TB and HIV infection is known to occur.
Enteric infections
In the presence of immunodeficiency due to HIV infection, bacterial gastrointestinal infections, in particular salmonella, shigella and Campylobacter are frequently more severe, commonly are accompanied by bacteraemia, and often relapse after antimicrobial therapy is discontinued. Clinical presentation may vary between mild diarrhoeal symptoms and severe abdominal pain and fever with or without diarrhoea. In immunocompetent individuals, bacterial gastroenteritis is generally a self-limited disease and anti-microbial therapy is not recommended. If organisms are isolated from blood cultures and the presentation is severe, underlying HIV infection should be considered and antimicrobial therapy administered.
Previously known as AIDS related complex or ARC, this term has become obsolete and symptomatic HIV infection is now preferred. This encompasses the generalized symptoms common in early to mid HIV infection such as night sweats, persistent generalized lymphadenopathy, skin manifestations and lethargy.
Diarrhoeal illness
Symptoms of diarrhoea are commoner at all stages of HIV infection compared with the rest of the population. In early disease, they often resemble Irritable Bowel Symdrome with no infection found and often spontaneous resolution. With increasing immune compromise, chronic diarrhoea, often in conjunction with weight loss supervenes and in 80% of patients a pathogen is isolated either from stool analysis or at OGD. The majority of these are either protozoa such as cryptosporidia, microsporidia, or isospora or viruses e.g. CMV. Any of the above found in the setting of chronic diarrhoea and weight loss should alert suspicion of HIV infection and each would constitute an AIDS diagnosis/
Many patients with advancing HIV infection lose weight. This most often occurs as a result of an intercurrent infection or anorexia associated with gastrointestinal disease, e.g. chronic diarrhoea.
1) Kaposis sarcoma
Currently there exist 4 categories of KS: classic (rare, seen in eastern Europe, Italy and Russia), endemic Africa, iatrogenic (e.g. in transplant recipients), and AIDS-associated. The clinical features of AIDS-associated KS are markedly different from those seen in the other forms. The disease is characterized by a multifocal widerspread distribution that may involve any location on the skin or mucous membranes, as well as the lymph nodes, GI tract and visceral organs. It can present at any stage of HIV infection and it tends to progress with increasing immunosuppression. In Africa, AIDS-associated KS appears to be transmitted by heterosexual contact and has an approximately equal incidence among men and women. This is in contrast to the male predominance observed in all other population.
2) Lymphoma
Between 3 and 10% of AIDS patients will develop Non-Hodgkins Lymphoma (NHL) at some stage of their disease. AIDS associated NHL differs in several respects from NHL in immunocompetent patients: the lymphomas often involve extranodal sites and primary central nervous system (CNS) lymphomas are common.
5) Cervical and anal intra-epithelial neoplasia
Women with HIV have a higher risk of cervical intra-epithelial neoplasia and a higher rate of infection with HPV. Although this increase is related to immunosuppression, it has also been observed in the early stages of HIV disease. Whilst cervical cancer is more common in groups with a high HIV prevalence (and was designated an AIDS difining diagnosis in 1993) HIV has not been shown to increase the frequency of this cancer.
The same findings are true of anal intra-epithelial dysplasia and anal cancer, most common in gay men.